Positioning accuracy of a single-isocenter multiple targets SRS treatment: A comparison between Varian TrueBeam CBCT and Brainlab ExacTrac

PurposeThis study compared the positioning accuracy between cone-beam CT (CBCT) and ExacTrac (ETX) for a single-isocenter multiple target stereotactic radiosurgery (SRS) on two TrueBeam STx systems.MethodsA single-isocenter treatment plan was simulated on an anthropomorphic head phantom with six spherical steel ball bearings (BBs). One of the BBs was chosen to be the isocenter. The five off-isocenter targets were located at various distances from the isocenter. MV portal images were generated to evaluate the deviations between the expected and the real center of the targets after CBCT and ETX positioning, respectively.ResultsThe evaluation of the positioning accuracy for the isocenter target showed that CBCT and ETX positioning provided comparable, sub-millimetric results. Deviations in positioning accuracy were also calculated for all other targets, also showing comparable results for CBCT and ETX. Moreover, our study showed that the deviation between CBCT and ETX positioning were in better agreement for TBSTx1 and deviated slightly higher on TBSTx2 (maximum: 1.23 mm at S/I direction), due to a less perfect alignment between the CBCT coordinate system and the ETX coordinate system on TBSTx2 compared to TBSTx1. This study also showed a correlation between the target positioning accuracy and the distance to the isocenter.ConclusionThe positioning accuracy of ETX and CBCT for targets located at isocenter and off-isocenter locations was compared on two treatment machines and found comparable. Our study highlights the importance of a proper calibration procedure, to ensure correct alignment between the CBCT, ETX and machine coordinate systems.     

Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology

The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.^1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema.^4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor.⁶ In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix.⁷ The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid.Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion.⁸ It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used.⁹.The aim of this video article is to demonstrate the detection of the SLN using intraoperative fluorescence imaging in patients with cervical and vulvar cancer. Fluorescence imaging is used in conjunction with the standard procedure, consisting of radiocolloid and a blue dye. In the future, intraoperative fluorescence imaging might replace the current method and is also easily transferable to other indications like breast cancer and melanoma.     

Feasibility of image quality improvement for high-speed CBCT imaging using deep convolutional neural network for image-guided radiotherapy in prostate cancer

PurposeHigh-speed cone-beam computed tomography (CBCT) scan for image-guided radiotherapy (IGRT) can reduce both the scan time and the exposure dose. However, it causes noise and artifacts in the reconstructed images due to the lower number of acquired projection data. The purpose of this study is to improve the image quality of high-speed CBCT using a deep convolutional neural network (DCNN).MethodsCBCT images of 36 prostate cancer patients were selected. The CBCT images acquired at normal scan speed were defined as CBCT_100%. Simulated high-speed CBCT images acquired at twofold and fourfold scan speed were created, which were defined as CBCT_50% and CBCT_25%, respectively. The image quality of the CBCT_50% was treated as the requirement for IGRT in this study because previous studies reported that its image is sufficient with respect to IGRT. The DCNN model was trained to learn direct mapping from CBCT_25% to the corresponding CBCT_100%. The performance of the DCNN model was evaluated using the sixfold cross-validation method. CBCT images generated by DCNN (CBCT_25%+DCNN) were evaluated for voxel value accuracy and image quality.ResultsThe DCNN model can process CBCT_25% of a new patient within 0.06 s/slice. The CBCT_25%+DCNN was comparable to the CBCT_50% in terms of both voxel value accuracy and image quality.ConclusionsWe developed a DCNN model to remove noise and artifacts from high-speed CBCT. We emphasize that it is possible to reduce exposure to one quarter and to increase the CBCT scan speed by a factor of four.     

Preliminary analysis for integration of spot-scanning proton beam therapy and real-time imaging and gating

PurposeSpot-scanning proton beam therapy (PBT) can create good dose distribution for static targets. However, there exists larger uncertainty for tumors that move due to respiration, bowel gas or other internal circumstances within the patients. We have developed a real-time tumor-tracking radiation therapy (RTRT) system that uses an X-ray linear accelerator gated to the motion of internal fiducial markers introduced in the late 1990s. Relying on more than 10 years of clinical experience and big log data, we established a real-time image gated proton beam therapy system dedicated to spot scanning.Materials and methodsUsing log data and clinical outcomes derived from the clinical usage of the RTRT system since 1999, we have established a library to be used for in-house simulation for tumor targeting and evaluation. Factors considered to be the dominant causes of the interplay effects related to the spot scanning dedicated proton therapy system are listed and discussed.Results/conclusionsTotal facility design, synchrotron operation cycle, and gating windows were listed as the important factors causing the interplay effects contributing to the irradiation time and motion-induced dose error. Fiducial markers that we have developed and used for the RTRT in X-ray therapy were suggested to have the capacity to improve dose distribution. Accumulated internal motion data in the RTRT system enable us to improve the operation and function of a Spot-scanning proton beam therapy (SSPT) system. A real-time-image gated SSPT system can increase accuracy for treating moving tumors. The system will start clinical service in early 2014.     

Temperature-sensitive paramagnetic liposomes for image-guided drug delivery: Mn versus [Gd(HPDO3A)(H2O)]

Temperature-sensitive liposomes (TSLs) loaded with doxorubicin (Dox), and Magnetic Resonance Imaging contrast agents (CAs), either manganese (Mn^2 +) or [Gd(HPDO3A)(H₂O)], provide the advantage of drug delivery under MR image guidance. Encapsulated MRI CAs have low longitudinal relaxivity (r₁) due to limited transmembrane water exchange. Upon triggered release at hyperthermic temperature, the r₁ will increase and hence, provides a means to monitor drug distribution in situ. Here, the effects of encapsulated CAs on the phospholipid bilayer and the resulting change in r₁ were investigated using MR titration studies and ¹H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles. Our results show that Mn^2 + interacted with the phospholipid bilayer of TSLs and consequently, reduced doxorubicin retention capability at 37 °C within the interior of the liposomes over time. Despite that, Mn^2 +-phospholipid interaction resulted in higher r₁ increase, from 5.1 ± 1.3 mM^− 1 s^− 1 before heating to 32.2 ± 3 mM^− 1 s^− 1 after heating at 60 MHz and 37 °C as compared to TSL(Gd,Dox) where the longitudinal relaxivities before and after heating were 1.2 ± 0.3 mM^− 1 s^− 1 and 4.4 ± 0.3 mM^− 1 s^− 1, respectively. Upon heating, Dox was released from TSL(Mn,Dox) and complexation of Mn^2 + to Dox resulted in a similar Mn^2 + release profile. From 25 to 38 °C, r₁ of [Gd(HPDO3A)(H₂O)] gradually increased due to increase transmembrane water exchange, while no Dox release was observed. From 38 °C, the release of [Gd(HPDO3A)(H₂O)] and Dox was irreversible and the release profiles coincided. By understanding the non-covalent interactions between the MRI CAs and phospholipid bilayer, the properties of the paramagnetic TSLs can be tailored for MR guided drug delivery.     

图像引导下精确放疗治疗宫颈癌的价值分析

摘要 目的：探讨与分析图像引导下精确放疗治疗宫颈癌的价值。方法：2016年1月至2017年12月选择在本院进行诊治的宫颈癌患者120例,根据治疗方法的不同把患者分为观察组80例与对照组40例。对照组给予常规放疗方法,观察组给予图像引导下精确放疗,记录与随访两组的预后情况。结果：治疗后观察组的总有效率为85.0 %,显著高于对照组的60.0%(P<0.05)。观察组治疗期间的放射性直肠损伤、放射性膀胱损伤、消化道反应、血液系统反应等毒副反应发生率显著低于对照组(P<0.05)。观察组治疗后的IgG与IgA值都显著高于治疗前(P<0.05),也高于对照组(P<0.05),对照组治疗前后对比差异无统计学意义(P>0.05)。Kapplan-meier法分析显示观察组的无疾病进展生存时间和总生存时间都显著长于对照组(P<0.05)。结论：图像引导下精确放疗治疗宫颈癌能促进患者免疫功能的恢复,提高治疗效果与减少毒副反应的发生,从而延长患者的生存时间。     

SBRT targets that move with respiration

The technology of treating SBRT targets that move with respiration has undergone profound changes over the last 20 years. This review article summarizes modern image guidance to localize the target in real-time to account for intra-fraction motion. The state-of-the art respiratory motion compensation techniques will be discussed, including the determination and application of appropriate margins. This includes compression, gating and breath-hold, including the use of audiovisual feedback to manage motion. Approaches to real-time tracking include the use of hybrid external-internal imaging to build a skin-to-tumor correlation, which can then be tracked with a mobile robot (CyberKnife Synchrony, clinical since 2003) as well as the use of non-ionizing electromagnetic tumor surrogate localization followed by real-time tracking with a moving MLC (in clinical trials in Europe and Australia). Lastly, the clinical application of real-time MRI soft-tissue imaging to deliver adaptive, iso-toxic treatments will be presented.     

Automatic tracking of gold seed markers from CBCT image projections in lung and prostate radiotherapy

PurposeTo construct a method and software to track gold seed implants in prostate and lung patients undergoing radiotherapy using CBCT image projections.MethodsA mathematical model was developed in the MatLab (Mathworks, Natick, USA) environment which uses a combination of discreet cosine transforms and filtering to enhance several edge detection methods for identifying and tracking gold seed fiducial markers in images obtained from Varian (Varian Medical Systems, Palo Alto, USA) and Elekta (Kungstensgatan, Sweden) CBCT projections.ResultsOrgan motion was captured for 16 prostate patients and 1 lung patient.ConclusionImage enhancement and edge detection is capable of automatically tracking markers for up to 98% (Varian) and 79% (Elekta) of CBCT projections for prostate and lung markers however inclusion of excessive bony anatomy (LT and RT LAT) inhibit the ability of the model to accurate determine marker location.     

Adjuvant gamma knife surgery and image-guided,intensity-modulated radiation therapy for the treatment of sacral chordomas

AimThe aim of this study was to confirm whether patients with sacral chordoma benefit from adjuvant radiotherapy and to determine the optimal photon radiotherapy module for comprehensive treatment.BackgroundChordoma is a rare slow-growing neoplasm arisen from cellular remnants of the notochord. About 50% occur in the sacrococcygeal region. Surgical resection and adjuvant radiation therapy are recommended treatment due to the improving local control rate.Materials and methods118 patients treated by surgery and adjuvant radiotherapy from August 2003 to May 2015 were retrospectively analyzed. All patients received surgical resection after diagnosis. Among these patients, 44 were treated by exclusive surgery, and 48 were treated with adjuvant image-guided, intensity-modulated radiation therapy (IG-IMRT). In addition, 26 patients were treated with gamma knife surgery (GKS) after surgical resection. The median follow-up was 54 months for all patients. Kaplan–Meier analysis was used to calculate recurrence-free survival (RFS) overall survival (OS).ResultsPatients treated with adjuvant radiotherapy had better RFS (p = 0.014) than those treated exclusively by surgery. The patients in the IG-IMRT group exhibited better recurrence-free survival (p = 0.01) than the GKS group. Moreover, in the IG-IMRT group, patients treated by higher dose were associated with better RFS (p = 0.04). No significant difference in OS was found. No grade 3 late toxicity was found.ConclusionsWe confirmed that adjuvant radiotherapy improved RFS but not OS in sacral chordoma patients after surgery. Furthermore, favorable RFS and low adverse event rates were observed following IG-IMRT. Our results suggest that high dose IG-IMRT is an appropriate module of adjuvant radiotherapy for sacral chordoma patients.     

Cone-beam CT-based inter-fraction localization errors for tumors in the pelvic region

PurposeTo evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed.MethodsData of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3.ResultsThe systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14 mm in the AP, 10 mm in the LL and 9–9.5 mm in the SI directions for the prostate and the gynecological groups and 9.5–10.5 mm in AP, 9 mm in LL and 8–10 mm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger.Conclusionswithout IGRT, large CTV-to-PTV margins up to 15 mm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.